Multi-Functional Cryogenic Storage Vessel

Abstract

Systems and devices with enhanced stability to kinetic impact for the containment of cryogenically preserved material. A device comprising a vessel with increased surface to volume ratio when compared to cylindrical vessels of like capacity, and further comprising a material that remains resistant to shock and impact at cryogenic temperatures while providing a continuous barrier of a single material surrounding the vessel contents. The device further comprising a design that may be readily modified to include internalized sensors, enhanced interfacing to external instruments, provide optimized thaw rate, and post-thawing sample processing capabilities.

Description

FIELD OF THE INVENTION[0001]This invention relates to vessel devices that securely contain frozen cell suspensions at cryogenic temperatures while also providing enhanced protection from impact, shock, and acceleration damage. The invention also pertains to cryogenic storage vessels having sensors and communication interfaces. In addition, the invention relates to cryogenic storage vessels that facilitate the interaction of the vessels with other devices during storage, transport, the thawing process, and after the thawing process. Lastly, the invention relates to cryogenic storage vessels configured to accommodate fluidic procedures and cell processing in a container stored within the vessel and prior to removal of the vessel contents after thawing.BACKGROUND OF THE INVENTION[0002]The field of live-cell based pharmacology has been well established and will continue to expand and advance further in the future. Many of the cell-based therapeutics require cell populations to be expand...

AI Technical Summary

Benefits of technology

[0009]The present invention relates generally to devices that provide for the containment of liquid samples that are subsequently frozen and stored for the purpose of cryopreservation. In the first aspect, the present invention is directed to cryogenic storage vessels that provide protection from impact, shock, and acceleration or damage due to applied mechanical forces, wherein, upon filling and sealing the storage vessel, the storage vessel comprises a complete and continuous interior surface comprised of a single material that is joined in a seam closed by a fusion bond. In some instances, the vessels are constructed from cryogenic-compatible materials that provide toughness, reduced embrittlement, maximize flexibility and resistance to shock and stress fracture at cryogenic temperatures, while being sufficiently flexible and pliant at ambient and aqueous solution freezing temperatures to allow limited adjustment to the volumetric capacity by compressive mechanical forces or by expansion pressure of the aqueous contents upon solidification. In some instances, the invention provides for cryogenic storage vessels that are semi-rigid such that the dimensions of the vessel do not collapse in the gravitational field, thereby preventing inner surface tensions that result in retention of liquids contained therein upon emptying.

[0010]Some instances of the invention provide varied dimension to control a surface-to-volume ratio of the vessel. For example, in some instances one dimension of the vessel is minimized while the remaining two dimensions are adjusted to optimize the area of flat surfaces on two major parallel planes, thereby controlling the surface to volume ratio such that contact of the larger planar surfaces with an external planar heat sink or heat source provides a rapid transition time between cryogenic temperatures and the melting temperature of the vessel contents. To allow for expansion of aqueous contents during freezing and to provide for the option of minimizing air void while filling the vessels, some embodiments of the invention provide one or more rim expansion curvatures that allow an increase in a separation distance of at least two major vessel surfaces, while maintaining a parallel planar orientation of the major vessel surfaces. In some instances, a first dimension of the vessel is made smaller than the remaining two dimensions of the vessel, wherein the two major dimensions control an area of a major surface on each vessel shell part, where a third dimension controls a distance between the major surface of each shell part when the vessel is assembled. In some embodiments, a ratio between a first dimension and a combined dimension of a second dimension and a third dimension is from 1:1 to 4:1. In some embodiments, a ratio between a first dimension and a third dimension is from 1:1 to 30:1. In some embodiments, a ratio between a first dimension and a third dimension is from 2:1 to 20:1. In some embodiments, a vessel of the present invention comprises an area determined by a first dimension and a second dimension, wherein the area is from 3 cm2 to 300 cm2, or from 300 cm2 to 1000 cm2.

[0014]In some instances, a vessels comprises one or more access ports that are located away from one or more midline seams, offset seams, or minor surfaces of the vessel, thereby protecting the access ports from impact, shock, or unintentional mechanical distortions or stresses. In some instances, the access ports comprise an integrated port, wherein the integrated port is an uninterrupted continuation of the vessel wall material, thereby providing an access port seal that is not reliant upon bonded seams of either like or unlike materials. In some instances, no additional construction of access ports is necessary beyond a molding of specific depressions or curvature in the vessel surface, while in other instances, access to the contents of the vessel may be achieved by directly penetrating a wall surface of the vessel. In some instances, a recess that serves as an access port in a surface of the vessel may be occluded by a removable membrane, wherein following sterilization of the finished vessel, the membrane maintains a sterile state of the access port until the membrane is removed.

[0016]In a third aspect of the invention, a vessel is provided that comprises an external wall constructed from two opposing parts joined at a median plane seam, and where one dimension of the vessel is smaller than the remaining two dimension such that the vessel has two large planar surfaces joined by a swept rim wall that terminates in a flange seam joined in a heat weld, and additional seams that form a seal division of the vessel and that also join with swept rims through the interior portion of the vessel such that the vessel is divided into two or more compartments that are completely isolated from one another except at specific locations where through-ducts may allow communication between the two separate enclosed compartments or volumes. In some instances, one or more through-ducts are normally occluded by a valve mechanism In some instances, a valve opens when the vessel is subjected to sufficient centrifugal force aligned with a specific vector. In some instances, a method for using a vessel of the present invention comprising steps for filling a first cavity of a vessel with a cell suspension containing a cryopreservation fluid, and filling a second cavity of the vessel with an exchange medium, wherein upon thawing the cryopreservative medium, cells are transferred from the first cavity and into the second cavity, whereby the cryopreservative medium is substantially diluted or absent. In some instances, the cells in the first cavity of the vessel are promoted through one of the ducts by a centrifugal force at the same time that the same centrifugal force promotes the opening of the duct communicating with the first and second cavity, thereby allowing passage of the cells into the second cavity. In some instances, a second communication duct joining the first cavity and the second cavity is occluded by a valve that is located proximal to the axis of rotation at which an angular displacement creates a centrifugal force upon the vessel. At a sufficient level of relative centrifugal force, the valve in the second communication duct is opened, and being proximal to the remainder of the vessel, and as liquid contents of the vessel will be displaced to the distal portion of the vessel, the open second communication duct valve allows gas pressure to equilibrate between the two vessel chambers, thereby eliminating any pressure differential between the two chambers when the centrifugal force is absent.

Problems solved by technology

In some instances, the vessels are constructed from cryogenic-compatible materials that provide toughness, reduced embrittlement, maximize flexibility and resistance to shock and stress fracture at cryogenic temperatures, while being sufficiently flexible and pliant at ambient and aqueous solution freezing temperatures to allow limited adjustment to the volumetric capacity by compressive mechanical forces or by expansion pressure of the aqueous contents upon solidification.

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